A cross-sectional study was conducted to evaluate possible interregional differences in respiratory health in primary school children living in two different towns of the Netherlands, Melick/Herkenbosch Asenray (MHA) (n = 511) and Leek (LK) (n = 612). The prevalence of respiratory symptoms was determined by means of a questionnaire and respiratory impedance was measures using the forced oscillation technique (FOT). Respiratory symptoms were reported consistently more often in MHA than in LK; chronic cough (17% MHA vs 5% LK), shortness of breath (15% vs 8%), wheeze (16% vs 13%) and attacks of shortness of breath with wheeze (10% vs 7%). However, doctor-diagnosed asthma was reported as 7% in MHA and 6% in LK. The prevalence rates expressed as odds ratios of MHA versus LK were all > 1 even when adjusted for known indoor environmental factors. Living in MHA appeared to be a statistically significant determinant of the reported symptom prevalence. Furthermore, the child's age, maternal smoking (> 10 cigarettes/day), and having had domestic animals were positively associated with one or more respiratory symptoms. Calculating adjusted differences in respiratory impedance between the regions resulted in a small but statistically significant difference in resonant frequency, LK being slightly at a disadvantage. Measured outdoor air pollution levels of SO2, NO2, O3 and PM10 were in general higher in MHA. In both regions however, the average levels remained below the present WHO guidelines, except for NO2 in MHA where the guideline was slightly exceeded. CONCLUSION: In this study prevalence rates of key symptoms of asthma were found to be significantly higher in children living in one region of the Netherlands (MHA) compared to another (LK). Known (indoor) risk factors for respiratory disease could not explain the observed differences in symptom prevalence between the regions. However, statistically but not clinically significant interregional differences in respiratory impedance values were found between children living in MHA and children living in LK. Further research will have to incorporate techniques to evaluate the potential influence of information bias.